Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab.

HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological "ultrahigh" ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1-9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1-12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.

Crystal Chemistry and Photoluminescent Aspects of Bright Orange Light Emitting Sm3+- Activated Ba2BiV3O11 Nanomaterials for Advanced Illuminating Applications.

In the present system, Sm3+ activated Ba2BiV3O11 nanomaterial series radiating orange-red light was developed via an efficient approach of solution combustion method. The structural examinations using XRD analysis indicate that the sample is crystallized into the monoclinic phase with the P21/a (14) space group. The elemental composition and morphological conduct were studied via energy dispersive spectroscopy (EDS) and scanning electron microscopy (SEM) respectively. Also, the formation of nanoparticles was confirmed by transmission electron microscopy (TEM). Photoluminescent (PL) examinations reveal the orange-red emission from the developed nanocrystals via documenting the emission spectra, which reveals the peak at 606 nm due to the 4G5/2 → 6H7/2 transition. Further, the decay time, non-radiative rates, quantum efficiency, and band gap of the optimal sample were computed as 1.3263 ms, 219.5 s- 1, 70.88%, and 3.41 eV respectively. Finally, the chromatic parameters including color - coordinates (0.5565, 0.4426), 1975 K color correlated temperature (CCT), and color purity (85.58%) reflected their excellent luminous performance. The above-mentioned outcomes endorsed the relevancy of the developed nanomaterials as a propitious agent in the engineering of advanced illuminating optoelectronic appliances.

Crystal Phase Refinement and Optical Features of Highly Efficient Green Light Radiating Ca9Y(VO4)7: Er3+ Nanophosphors for Emerging Solid-state Lighting Applications.

Ca9Y(VO4)7 phosphor activated with Er3+ ions have been developed by the urea-aided solution combustion technique. XRD profiles assisted with Rietveld refinement executed over-developed Er3+-activated Ca9Y(VO4)7 powder, revealed a trigonal phase with the R3c space group. The electron microscope techniques namely TEM and SEM characterize the size and surface-linked qualities of the developed nanopowder, respectively. The uniform distribution of various elements in the nanocrystalline sample is authenticated by an energy-dispersive spectroscopy (EDS) system. The Eg (band gap) value of 3.64 eV for Ca9Y0.9Er0.1(VO4)7 and 3.74 eV for Ca9Y(VO4)7 has been estimated. Upon 382 nm excitation, Er3+: Ca9Y(VO4)7 phosphor gives rise to the bright green emission owing to the 4S3/2 → 4I15/2 transition. The concentration quenching after 10 mol% composition of trivalent erbium ions is attributed to dipole-dipole interlinkages in accordance with Dexter's theory. The radiative lifetime (1.1083 ms), non-radiative rates (0.2079 ms- 1), quantum efficiency (79%), along with colorimetric parameters i.e. CIE x (= 0.2577), y (= 0.4566), and CCT quantities offer Ca9Y0.9Er0.1(VO4)7 as a proficient green radiating nanomaterial for RGB phosphors in solid-state applications.

CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer.

OBJECTIVE: To investigate CITED1 as a potential biomarker of anti-endocrine response and breast cancer recurrence, given its previously determined role in mediating estrogen-dependant transcription. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development. RESULTS: CITED1 mRNA is associated with estrogen-receptor positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen response. The effect was particularly evident in the subset of estrogen-receptor positive, lymph-node negative (ER+/LN-) patients although noticeable divergence of the groups was apparent only after five years. Tissue microarray (TMA) analysis further validated the association of CITED1 protein, by immunohistochemistry, with favourable outcome in ER+, tamoxifen-treated patients. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. Finally, MCF7 cells overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy. These findings together confirm the proposed mechanism of action of CITED1 and support its potential use as a prognostic biomarker.

Combustion Synthesis and Study of Double Charge Transfer in Highly Efficient Cool White-emitting Dy3+ Activated Vanadate-based Nanophosphor for Advanced Solid-state Lighting.

A series of Ca9Gd(VO4)7: Dy3+ (x = 0.01-0.20) nanophosphor crystals emitting a cool white light were synthesized by solution combustion methodology. The X-ray diffraction patterns were analyzed and processed using Rietveld refinement. The fabricated nanophosphor was found to crystallize in a trigonal crystal lattice with space group R3c(161). The morphological behavior of the prepared nanophosphor was investigated using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The photoluminescence properties of the nanophosphor correspond to cool white emission upon near-ultraviolet (NUV) excitation at 327 nm due to 4F9/2 → 6H15/2 (bluish) and 4F9/2 → 6H13/2 (yellowish) radiative relaxations at 487 nm and 576 nm respectively. Also, there is a strong occurrence of double charge transfer from O2- ions to Dy3+ and V5+ ions with the latter being stronger due to the high positive charge of V5+ ions. Color coordinates (x = 0.2878, y = 0.3259) are consistent with white emission. Auzel's model was implemented to examine the non-radiative relaxation (113.5 ms-1), radiative lifetime (1.4856 ms), and quantum efficiency (83.13%) values. The crystalline and optical behavior of the synthesized cool white emitting nanophosphor facilitates its use in near-UV-based WLEDs and other advanced solid-state lighting.

Clinical associations of ESR2 (estrogen receptor beta) expression across thousands of primary breast tumors.

Estrogen receptor alpha (ERα, encoded by ESR1) is a well-characterized transcription factor expressed in more than 75% of breast tumors and is the key biomarker to direct endocrine therapies. On the other hand, much less is known about estrogen receptor beta (ERß, encoded by ESR2) and its importance in cancer. Previous studies had some disagreement, however most reports suggested a more favorable prognosis for patients with high ESR2 expression. To add further clarity to ESR2 in breast cancer, we interrogated a large population-based cohort of primary breast tumors (n = 3207) from the SCAN-B study. RNA-seq shows ESR2 is expressed at low levels overall with a slight inverse correlation to ESR1 expression (Spearman R = -0.18, p = 2.2e-16), and highest ESR2 expression in the basal- and normal-like PAM50 subtypes. ESR2-high tumors had favorable overall survival (p = 0.006), particularly in subgroups receiving endocrine therapy (p = 0.03) and in triple-negative breast cancer (p = 0.01). These results were generally robust in multivariable analyses accounting for patient age, tumor size, node status, and grade. Gene modules consistent with immune response were associated to ESR2-high tumors. Taken together, our results indicate that ESR2 is generally expressed at low levels in breast cancer but associated with improved overall survival and may be related to immune response modulation.